Hyaluronic acid, which is also referred to as hyaluronan or “HA,” is a naturally occurring, water soluble polysaccharide that is a major component of the extracellular matrix and is widely distributed in animal tissues. Naturally-occurring HA generally has a molecular weight range of between about 6×104 to about 8×106 Daltons. It has excellent biocompatibility and does not produce a foreign body or allergic reaction when implanted into a subject.
Methods of preparing commercially available hyaluronan are known. Further, many forms of HA have been employed, for example as surgical aids to prevent post operative adhesions of tissues, as adjuncts to synovial fluid in joints, as fluid replacement and/or surgical aids in ophthalmic surgery, as a scaffold for tissue engineering in vitro or guided tissue regeneration or augmentation in vivo, and the like.
Hyaluronic acid (HA) gel products have been injected into joints for arthritis and superficially into the skin to treat wrinkles. In the skin they are typically injected as tiny drops or feathered into the skin as fine lines in the layer called the dermis. The skin is divided into the epidermis the most outer layer and then the dermis and then the fat and lastly the muscle and or bone. If one injects into the fat using the above techniques with the available commercial products, it is expected that the material will disappear quickly because the body breaks down the material with a naturally occurring enzyme called hyaluronidase. HA that is deposited in the form of relatively small microdroplets or feathered lines can be readily broken down by hyaluronidase.
Previous attempts to inject a small amount of hyaluronic acid material along the ridge of the bone have been made, but they generally use a small amount of hyaluronic acid material to try to soften the appearance of grooves, such as those that commonly occur under the eyes.
Recently, in 2006, a deep form of HA treatment using a larger molecule of HA was approved in 2006 for injection into deep tissues using a large bore needle. However, this technique requires a surgical incision to permit entry of the needle. The longevity of this treatment is presently believed to be about 1 year.
Accordingly, none of the above-mentioned techniques provides long-term methods for minimizing the appearance of deep wrinkles or folds in the skin by administering bolus injections of hyaluronic acid. There is a need in the art for long-term, non-surgical methods that are useful for reducing or eliminating undesirable folds or wrinkles of the skin.